BIOMATERIALS
·
2024
·
IF 12.8
Di Ge,Siqi Ma,Tingting Sun,Yunfei Li,Jiaxing Wei,Chenao Wang,Xiaoyuan Chen,Yonghong Liao
Despite the recognized potential of inhaled nanomedicines to enhance and sustain local drug concentrations for lung cancer treatment, the influence of macrophage uptake on targeted nanoparticle delivery to and within tumors remains unclear. Here, we developed three ligand-coated nanoparticles for pulmonary delivery in lung cancer therapy: phenylboronic acid-modified nanoparticles (PBA-NPs), PBA combined with folic acid (FA-PBA-NPs), and PBA with mannose (MAN-PBA-NPs). In vitro, MAN-PBA-NPs were preferentially internalized by macrophages, whereas FA-PBA-NPs exhibited superior uptake by cancer cells compared to macrophages. Following intratracheal instillation into mice with orthotopic Lewis lung carcinoma tumors, all three nanoparticles showed similar lung retention. However, MAN-PBA-NPs were more prone to interception by lung macrophages, which limited their accumulation in tumor tissues. In contrast, both PBA-NPs and FA-PBA-NPs achieved comparable high tumor accumulation (∼11.3% of the dose). Furthermore, FA-PBA-NPs were internalized by ∼30% of cancer cells, significantly more than the 10–18% seen with PBA-NPs or MAN-PBA-NPs. Additionally, FA-PBA-NPs loaded with icaritin effectively inhibited the Wnt/β-catenin pathway, resulting in superior anti-tumor efficacy through targeted cancer cell delivery. Overall, FA-PBA-NPs demonstrated advantageous competitive uptake kinetics by cancer cells compared to macrophages, enhancing tumor targeting and therapeutic outcomes.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Zheng Liu,Wen-ting Dong,Wen-feng Wei,Jin-hai Huo,Wei-ming Wang
Ethnopharmacological relevance Traditional Chinese medicine categorizes Mycoplasma pneumoniae pneumonia as “lung heat”, and treatment with heat clear and detoxify. Traditional Chinese medicine believes that the lungs and intestines come from the same source, and the intestine is related to pneumonia. This is the same as the gut-lung axis theory. Qinbaiqingfei concentrate pills (QBs) were modified based on Cough San in the ancient medical book Medical Awareness . It clears lung heat, moisturizes the lungs and dredges collaterals, and has a good ability to treat Mycoplasma pneumoniae . Aim of the study A rat model of Mycoplasma pneumoniae was established. From the aspect of intestinal flora and mucosal immunity, the potential mechanism of the QBs was researched. Materials and methods First, the content of Mycoplasma pneumoniae in lung tissue and the levels of the inflammatory factors IL-4, IL-10, TNF-α and INF-γ were detected. To determine the expression of NF-kB related proteins in lung tissue, which can understand the ability in treating disease. Next, metagenomic sequencing was performed to detect changes in short-chain fatty acids, proving the ability of the drug to regulate intestinal microecology. Finally, HDAC , LPS , SIgA, etc. were detected to facilitate the correlation of the overall experimental indicators. Results QBs reduces the levels of IL-4, IL-10, TNF-α and INF-γ in the serum by inhibiting the expression of MyD88 , IKKα, IκBα, and NF-κB p65 in lung tissue. In addition, QBs restores the ratio of gram-negative bacteria to gram-positive bacteria in the intestine, restores the secretion of acetic acid, propionic acid , butyric acid , isobutyric acid and isovaleric acid , and promotes the secretion of NF-κB p65 and SIgA by HDAC1/3. The result is that the lung tissue is repaired and the proliferation of Mycoplasma pneumoniae is inhibited. Conclusions From the “gut-lung axis”, a new research perspective was discovered. QBs intervened in the intestines and lungs to treat Mycoplasma pneumoniae .
研究领域:
民族药理学
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微生物学
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免疫学
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中医药
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药理学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xi Wang,Weimin Wan,Guiquan Liu,Tangjun Ren,John Osilama Thomas,Haonan Wu,Chen An,Fei Tian,Yan Zhu,Alexander Kros,Jian Yang
The complementary fusogenic coiled-coil lipopeptides CPE and CPK have gained attention as mediators of drug delivery via membrane fusion for various therapeutic applications. However, the models used in these studies were mainly 2D cell cultures and animal models, leaving the in-site interaction and physiological effects of this lipopeptide system in vivo unclear. To address this, we constructed two 3D cell models in vitro , a mimicking lung organ (mLO) using 3D printed hydrogel cell scaffold and alveolar organoids (AOs) derived from mouse adult stem cells. These models were used to evaluate the lipopeptide modified membrane fused drug delivery system (MF-DDS) and show the details of drug delivery in treating acute lung injury (ALI) model based on the 3D models. Our results revealed that MF-DDS demonstrated superior drug delivery efficiency in mLO, particularly when cultured dynamically on a chip compared to a static U-shaped plate. Importantly, the MF-DDS demonstrated great biocompatibility with no significant changes in macrophage phenotype, inflammatory cytokine secretion, and lung barrier integrity on the mLO after the cell membrane fused with the artificial lipid membrane. In the lipopolysaccharide (LPS) induced injury model using mLO, the MF-DDS delivered naringin effectively, significantly reduced inflammatory factor secretion, macrophage polarization, and protected lung barrier disruption. Furthermore, the safety and effectiveness of MF-DDS were validated using AOs, underscoring its potential in treating ALI. These findings offer critical insights into the interactions between MF-DDS and organ systems, paving the way for faster and more precise evaluations of drug delivery strategies for disease treatment.
研究领域:
药理学
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生物医学工程
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细胞生物学
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产品关联
DOI
高影响因子
BMC Pulmonary Medicine
·
2024
·Vol. 24
·期 1
·1-16
·
IF 2.6
Sun Lili,Liu Lihua,Liang Dongxue,Liu Linlin
Pulmonary hypertension (PH) is a chronic pulmonary vascular disease and causes massive deaths. Here, we intended to investigate the function and mechanism of SOCS5 in PH. We engineered a hypoxia-induced PH model in mice. HE staining were implemented to evaluate pathological alterations in the lung tissues. The potential mechanism of SOCS5 in regulating hypoxia-induced pulmonary artery smooth muscle cell (PASMC) function was explored in vitro. RT-qPCR and western blot revealed that the level of SOCS5 was decreased both in PH mice and hypoxia-induced HPASMCs. Functional assays were performed for confirming the role of SOCS5 in modulating the cell phenotype and JAK2/STAT3 pathway in HPASMCs. Results revealed that overexpression of SOCS5 suppressed proliferation, migration and contraction of HPASMCs and negatively regulated the JAK2/STAT3 signaling pathway in HPASMCs under hypoxia in vitro, while knockdown of SOCS5 accelerated it. As evidenced by mechanism studies, SOCS5 was targeted and regulated by miR-155-5p, hence affecting on HPASMC proliferation, migration and contraction. These outcomes indicated that the decreased level of SOCS5 in hypoxia-induced HPASMCs promoted the cell proliferation, cell migration, and cell contraction through activating JAK2/STAT3 signaling pathway. Moreover, SOCS5 was targeted by miR-155-5p. All in all, our work hinted that miR-155-5p/SOCS5/JAK2/STAT3 axis played a crucial part in PH.
研究领域:
心血管疾病
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分子生物学
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细胞生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
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IF 11.467
Siqi Ma,Zhaoqing Cong,Jiaxing Wei,Weiya Chen,Di Ge,Feifei Yang,Yonghong Liao
Very little is currently known about how inhaled nanomedicine for lung cancer treatment overcomes biological barriers hampering the tumor availability of drug and nanoparticles . Here, we developed a size-transformable nanocarrier (~ 119 nm) in which small-size nanoparticles (~ 28 nm) were loaded in the large nanocarrier after the addition of modified hyaluronan and could be released upon size-transformation at tumor tissue. Subsequently, the pulmonary and tumor pharmacokinetics of the two nanocarriers containing 7-ethyl-10-hydroxycamptothecin (SN38) and a covalently linked fluorescent sonosensitizer were comparatively investigated after intratracheal instillation to mice bearing orthotopic Lewis lung carcinoma tumors. The results showed that both instilled nanoparticles seemed to transport drug to tumor by direct access and transcytosis of nanoparticles, and diffusion of the released drug with the latter accounting for a great proportion of the drug tumor bioavailability. Relative to the small-size nanocarrier, the size-transformable counterpart appeared to restrict the mucociliary and absorption clearances from the lung and the clearance from the tumor interstitium to circulation, leading to increases in lung and tumor bioavailability of SN38 by 58.5% and 199%, respectively. In addition, the size-transformable nanoformulation conferred deep tumor penetration and sustained levels of both sonosensitizer and SN38 within tumors and simultaneously exerted sonodynamic- and chemo-therapies. Overall, the pulmonary delivery of size-transformable nanocarrier could co-deliver sonosensitizer and drug to deep tumor sites with enhanced tumor accumulation to realize combination therapy in lung cancer.
研究领域:
纳米医学
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癌症治疗
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2024
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IF 7.5
Yiheng Mao,Ying Chen,Yuan Li,Longda Ma,Xi Wang,Qi Wang,An He,Xi Liu,Tianyi Dong,Weina Gao,Yanfen Xu,Liang Liu,Liang Ren,Qian Liu,Peng Zhou,Ben Hu,Yiwu Zhou,Ruijun Tian,Zheng-Li Shi
As a primary target of severe acute respiratory syndrome coronavirus 2, lung exhibits heterogeneous histopathological changes following infection. However, comprehensive insight into their protein basis with spatial resolution remains deficient, which hinders further understanding of coronavirus disease 2019 (COVID-19)-related pulmonary injury. Here, we generate a region-resolved proteomic atlas of hallmark pathological pulmonary structures by integrating histological examination, laser microdissection, and ultrasensitive proteomics. Over 10,000 proteins are quantified across 71 post-mortem specimens. We identify a spectrum of pathway dysregulations in alveolar epithelium, bronchial epithelium, and blood vessels compared with non-COVID-19 controls, providing evidence for transitional-state pneumocyte hyperplasia. Additionally, our data reveal the region-specific enrichment of functional markers in bronchiole mucus plugs, pulmonary fibrosis, airspace inflammation, and alveolar type 2 cells, uncovering their distinctive features. Furthermore, we detect increased protein expression associated with viral entry and inflammatory response across multiple regions, suggesting potential therapeutic targets. Collectively, this study provides a distinct perspective for deciphering COVID-19-caused pulmonary dysfunction by spatial proteomics.
研究领域:
蛋白质组学
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肺科学
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病理学
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病毒学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Lifang Ye,Yu Zuo,Fang Chen,Yuetong Xu,Puli Zhang,Hongxia Yang,Qinglin Peng,Guochun Wang,Xiaoming Shu
Objective To evaluate adrenomedullin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of patients with dermatomyositis (DM) as well as their correlation with the severity of interstitial lung disease (ILD). Methods A total of 41 DM patients and seven immune-mediated necrotizing myopathy (IMNM) patients were recruited, in addition to 21 healthy controls (HCs). The adrenomedullin mRNA levels in PBMCs were measured via quantitative reverse-transcription real-time polymerase chain reaction (qRT-PCR). The associations between adrenomedullin expression levels and major clinical, laboratory, pulmonary function parameters and the prognosis of patients with DM-related ILD (DM-ILD) were analyzed. Immunohistochemical analysis was performed on lung tissues of DM-ILD patients to determine adrenomedullin expression. Results Adrenomedullin mRNA levels in PBMCs were significantly higher in DM patients than in IMNM patients and HCs (p = 0.022 and p<0.001, respectively). Among DM patients, the levels were significantly higher in those with rapidly progressive ILD (RP-ILD) than in those with chronic ILD (p = 0.002) or without ILD (p < 0.001). The adrenomedullin mRNA levels in DM-ILD were positively correlated with serum ferritin (r =0.507, p =0.002), lactate dehydrogenase (LDH) (r =0.350, p =0.045), and lung visual analog scale (VAS) (r=0.392, p=0.021) and were negatively correlated with pulmonary function test parameters, including predicted forced vital capacity (FVC)% (r = −0.523, p = 0.025), forced expiratory volume in 1 s (FEV1)% (r = -0.539, p = 0.020), and diffusing capacity of carbon monoxide (DLco)% (r = -0.495, p = 0.036). Immunohistochemical analysis of adrenomedullin confirmed higher expression in the alveolar epithelial cells and macrophages of DM patients with RP-ILD. Among the DM patients with ILD, the six decedents exhibited higher adrenomedullin levels than the 28 survivors (p = 0.042). The cumulative survival rate was significantly lower (62.5% vs . 100%, P = 0.005) in patients with an adrenomedullin level > 0.053 than in those with a level <0.053. Conclusions Adrenomedullin levels are upregulated in DM patients with RP-ILD and are associated with ILD severity and poor prognosis. Adrenomedullin may be a potential prognostic biomarker in DM patients with ILD, although need further investigation.
研究领域:
风湿病学
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肺科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Cancers
·
2024
·Vol. 16
·期 19
·3269
·
IF 4.5
Xinyue Zhao,Zhihui Han,Ruiying Liu,Zehao Li,Ling Mei,Yue Jin
Simple SummaryEpithelial-to-mesenchymal transition (EMT) plays a critical role in cancer progression, contributing to the invasive and migratory abilities of tumor cells. In this study, we show that FBXO11 promotes the degradation of ZEB1, a key EMT regulator, via ubiquitination. Loss of FBXO11 increases ZEB1 levels, enhancing the invasiveness of lung cancer cells, while its overexpression reduces ZEB1 and suppresses invasion. Importantly, higher FBXO11 expression is associated with better prognosis in non-small cell lung cancer (NSCLC), highlighting its potential role as a therapeutic target for controlling EMT and cancer metastasis.AbstractEpithelial-to-mesenchymal transition (EMT) affects the invasion and migration of cancer cells. Here, we show that FBXO11 recognizes and promotes ubiquitin-mediated degradation of ZEB1. There is a strong association between FBXO11 and ZEB1 in non-small cell lung cancer (NSLC) in a clinical database. FBXO11 interacts with ZEB1, a core inducer of EMT. FBXO11 leads to increased ubiquitination and proteasomal degradation of ZEB1. Depletion of endogenous FBXO11 causes ZEB1 protein accumulation and EMT in A549 and H1299 cells, while overexpression of FBXO11 reduces ZEB1 protein abundance and cellular invasiveness. Importantly, the depletion of ZEB1 suppresses the increased migration and invasion of A549 and H1299 cells promoted by the depletion of FBXO11. The same results are shown in xenograft tumors. High FBXO11 expression is associated with a favorable prognosis in NSLC. Collectively, our study demonstrates that FBXO11 modulates EMT by mediating the stability of ZEB1 in lung cancer cells.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2024
·
IF 3.3
Zhikun Zhang,Dawei Shi,Haiwei Dou,Ruijie Wan,Qing Yuan,Peng Tu,Deli Xin
In previous study, lower levels of serum GP130 were reported in children with MPP. GP130 is an important signal transducer, the down regulation of which may influence host immune responses. In this study, we aimed to analyze the regulatory mechanism of GP130 during MP infection. Firstly, the mRNA and protein levels of GP130 both decrease and then increase with increasing multiplicity of infection (MOI: 1 to 40) of MP. The lowest levels of GP130 were detected at MOI of 5. Then, heat treated MP but not trypsin treated MP or MP extracted proteins show regulatory effect to the expression of GP130. These indicate that the down regulation of GP130 is related to protein mediate adhesion process of MP. Gene expression analysis revealed that MP affected apoptosis and the TLR4 pathway in infected cells, and the mRNA level of IL-6 was correlated with that of GP130. Further, Z-VAD-FMK (pan-caspase inhibitor) can suppress the apoptosis induced by MP infection and restore GP130 at protein level. Further studies revealed that MP infection promoted TLR4 internalization but did not activate the NF-κB pathway. The levels of surface TLR4 showed correlation with the transcription of IL-6 and GP130. TAK242 (TLR4 inhibitor) and PS341 (proteasome inhibitor) can restore the decreased transcription of GP130, both of which were able to promote NF-κB pathway activation in MP-infected cells. These suggested that the regulation of TLR4/NF-κB pathway and induced apoptosis post MP infection are involved in the down-regulation of GP130 at transcription and protein levels, respectively.
研究领域:
微生物学
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免疫学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Gege Zeng,Zepeng He,Haihong Yang,Zhan Gao,Xueer Ge,Lixin Liu,Zhijia Liu,Yongming Chen
Much of current clinical interest has focused on mRNA therapeutics for the treatment of lung-associated diseases, such as infections, genetic disorders, and cancers. However, the safe and efficient delivery of mRNA therapeutics to the lungs, especially to different pulmonary cell types, is still a formidable challenge. In this paper, we proposed a cationic lipid pair (CLP) strategy, which utilized the liver-targeted ionizable lipid and its derived quaternary ammonium lipid as the CLP to improve liver-to-lung tropism of four-component lipid nanoparticles (LNPs) for in vivo mRNA delivery. Interestingly, the structure–activity investigation identified that using liver-targeted ionizable lipids with higher mRNA delivery performance and their derived lipid counterparts is the optimal CLP design for improving lung-targeted mRNA delivery. The CLP strategy was also verified to be universal and suitable for clinically available ionizable lipids such as SM-102 and ALC-0315 to develop lung-targeted LNP delivery systems. Moreover, we demonstrated that CLP-based LNPs were safe and exhibited potent mRNA transfection in pulmonary endothelial and epithelial cells. As a result, we provided a powerful CLP strategy for shifting the mRNA delivery preference of LNPs from the liver to the lungs, exhibiting great potential for broadening the application scenario of mRNA-based therapy.
研究领域:
药学
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纳米技术
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2022
·
IF 6.073
Wang Jia-Feng,Shi Chang-Yi,Ying Hua-Zhong
Antibiotic abuse is growing more severe in clinic, and even short-term antibiotic treatment can cause long-term gut dysbiosis, which may promote the development and aggravation of diseases. Cephalosporins as the broad-spectrum antibiotics are widely used for prevention and treatment of community-acquired respiratory tract infection in children. However, their potential consequences in health and disease have not been fully elaborated. In this study, the effects of cefaclor, cefdinir and cefixime on intestinal microbiota and lung injury were investigated in Streptococcus pneumoniae (Spn)-infected mice. The results showed that the proportion of coccus and bacillus in intestinal microbiota were changed after oral administration with cefaclor, cefdinir and cefixime twice for 10 days, respectively. Compared with the Spn-infected group, the proportion of Bifidobacterium and Lactobacillus in intestine were significantly reduced, while Enterococcus and Candida was increased after cephalosporin treatment. Furthermore, 3 cephalosporins could obviously increase the number of total cells, neutrophils and lymphocytes in BALF as well as the serum levels of endotoxin, IL-2, IL-1β, IL-6 and TNF-α. Mechanically, cephalosporins accelerated Spn-induced pulmonary barrier dysfunction via mediating the mRNA expressions of endothelial barrier-related proteins (Claudin 5, Occludin, and ZO-1) and inflammation-related proteins (TLR4, p38 and NF-κB). However, all of those consequences could be partly reversed by Bifidobacterium bifidum treatment, which was closely related to the elevated acetate production, indicating the protective effects of probiotic against antibiotic-induced intestinal dysbiosis. Therefore, the present study demonstrated that oral administration with cephalosporins not only disrupted intestinal microecological homeostasis, but also increased the risk of Spn infection, resulting in severer respiratory inflammation and higher bacterial loads in mice.
研究领域:
微生物学
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药理学
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免疫学
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呼吸病学
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感染性疾病
✓ 已验证
DOI
PubMed
高影响因子
Communications Biology
·
2025
·Vol. 8
·期 1
·1-14
·
IF 5.1
Sun Wei,Zhao Bo,He Zhong,Chang Lihua,Song Wei,Chen Yingying
Idiopathic pulmonary fibrosis (IPF) is an irreversible lung condition that progresses over time, which ultimately results in respiratory failure and mortality. In this study, we found that PLAC8 was downregulated in the lungs of IPF patients based on GEO data, in bleomycin (BLM)-induced lungs of mice, and in primary murine alveolar epithelial type II (pmATII) cells and human lung epithelial cell A549 cells. Overexpression of PLAC8 facilitated autophagy and inhibited apoptosis of pmATII cells and A549 cells in vitro. Moreover, inhibition of autophagy or overexpression of p53 partially abolished the effects of PLAC8 on cell apoptosis. ATII cell-specific overexpression of PLAC8 alleviated BLM-induced pulmonary fibrosis in mice. Mechanistically, PLAC8 interacts with VCP-UFD1-NPLOC4 complex to promote p53 degradation and facilitate autophagy, resulting in inhibiting apoptosis of alveolar epithelial cells and attenuating pulmonary fibrosis. In summary, these findings indicate that PLAC8 may be a key target for therapeutic interventions in pulmonary fibrosis.
研究领域:
呼吸病学
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细胞生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）